Abstract Selected for the 2006 Weinstein Cardiovascular Development Conference

The objective of the Weinstein Cardiovascular Development Conference is to advance the overall field of cardiovascular development via sharing information and facilitating collaborative investigations pertaining to normal and abnormal development of the heart and vasculature. Conference participants range from basic scientists, geneticists, pediatric cardiologists, adult cardiologists and biomedical engineers; totaling to as many as 400 attendees including scientists from Asia and Europe.

UA SBRP graduate student trainee, Patricia Caldwell will be presenting a talk titled: "Halogenated Hydrocarbons and Mechanisms of Cardio-Toxicity: A Genomic Approach" at the 2006 Weinstein Cardiovascular Development Conference that will be held May 11-13, 2006 in St. Pete Beach, FL. Below is the abstract for Ms. Caldwell’s platform presentation.

Halogenated Hydrocarbons and Mechanisms of Cardio-Toxicity: A Genomic Approach. 
PT Caldwell, PA Thorne, E Ferreira, RB Runyan¹ , and O Selmin.
Department of Veterinary Science & Microbiology and ¹Cell Biology and Anatomy, University of Arizona, Tucson, AZ.

Our laboratory has been investigating the molecular mechanisms used by halogenated hydrocarbons (HHs) to induce cardiac malformations in the embryonic heart. The HHs most commonly found in the environment are trichloroethylene (TCE), perchloroethylene (PCE), and trichloroacetic acid (TCA), their main metabolite. While TCE and PCE are used as solvents in industry and dry cleaning procedures, TCA is a common by-product of chlorination in municipal water supplies. Our hypothesis is that the effects of TCE, PCE and TCA on gene expression may be used as a tool for identifying the cellular pathways that are targeted by these toxicants during crucial phases of cardiac differentiation. Evaluation of experimental data obtained through different methodologies, including subtractive hybridization, real-time PCR, and microarray analysis, suggest that HHs cardio-toxicity may be mediated by alteration of genes involved in calcium signaling and DNA methylation pathways. In order to test these hypotheses, we selected a few genes as markers of HHs exposure and characterized their mode of action at the gene expression level. The selected molecules include Vimentin, a marker of cardiac differentiation; and Serca2a, which plays a major role on cardiac function through regulation of calcium concentration in the endoplasmic reticulum. Our results indicate a complex pattern of regulation at the transcript level that appears to be dose and toxicant specific.  TCA effects at the Serca2 promoter level support the hypothesis that DNA methylation may be disturbed by HHs.  Research in progress is investigating the effects of TCE and TCA on the methylation status of the Serca2 promoter, and on intracellular calcium fluxes. Current experiments are also testing the possibility to prevent or correct the negative action of these HHs on cardiac development using dietary supplementation.